Model of Brain Activation Predicts the Neural Collective Influence Map of the Brain

Efficient complex systems have a modular structure, but modularity does not guarantee robustness, because efficiency also requires an ingenious interplay of the interacting modular components. The human brain is the elemental paradigm of an efficient robust modular system interconnected as a network of networks (NoN). Understanding the emergence of robustness in such modular architectures from the interconnections of its parts is a long-standing challenge that has concerned many scientists. Current models of dependencies in NoN inspired by the power grid express interactions among modules with fragile couplings that amplify even small shocks, thus preventing functionality. Therefore, we introduce a model of NoN to shape the pattern of brain activations to form a modular environment that is robust. The model predicts the map of neural collective influencers (NCIs) in the brain, through the optimization of the influence of the minimal set of essential nodes responsible for broadcasting information to the whole-brain NoN. Our results suggest new intervention protocols to control brain activity by targeting influential neural nodes predicted by network theory.Comment: 18 pages, 5 figure

The effect of mode and context on survey results: analysis of data from the Health Survey for England 2006 and the Boost Survey for London.

BACKGROUND: Health-related data at local level could be provided by supplementing national health surveys with local boosts. Self-completion surveys are less costly than interviews, enabling larger samples to be achieved for a given cost. However, even when the same questions are asked with the same wording, responses to survey questions may vary by mode of data collection. These measurement differences need to be investigated further. METHODS: The Health Survey for England in London ('Core') and a London Boost survey ('Boost') used identical sampling strategies but different modes of data collection. Some data were collected by face-to-face interview in the Core and by self-completion in the Boost; other data were collected by self-completion questionnaire in both, but the context differed. Results were compared by mode of data collection using two approaches. The first examined differences in results that remained after adjusting the samples for differences in response. The second compared results after using propensity score matching to reduce any differences in sample composition. RESULTS: There were no significant differences between the two samples for prevalence of some variables including long-term illness, limiting long-term illness, current rates of smoking, whether participants drank alcohol, and how often they usually drank. However, there were a number of differences, some quite large, between some key measures including: general health, GHQ12 score, portions of fruit and vegetables consumed, levels of physical activity, and, to a lesser extent, smoking consumption, the number of alcohol units reported consumed on the heaviest day of drinking in the last week and perceived social support (among women only). CONCLUSION: Survey mode and context can both affect the responses given. The effect is largest for complex question modules but was also seen for identical self-completion questions. Some data collected by interview and self-completion can be safely combined

Defective Tmprss3-Associated Hair Cell Degeneration in Inner Ear Organoids

Mutations in the gene encoding the type II transmembrane protease 3 (TMPRSS3) cause human hearing loss, although the underlying mechanisms that result in TMPRSS3-related hearing loss are still unclear. We combined the use of stem cell-derived inner ear organoids with single-cell RNA sequencing to investigate the role of TMPRSS3. Defective Tmprss3 leads to hair cell apoptosis without altering the development of hair cells and the formation of the mechanotransduction apparatus. Prior to degeneration, Tmprss3-KO hair cells demonstrate reduced numbers of BK channels and lower expressions of genes encoding calcium ion-binding proteins, suggesting a disruption in intracellular homeostasis. A proteolytically active TMPRSS3 was detected on cell membranes in addition to ER of cells in inner ear organoids. Our in vitro model recapitulated salient features of genetically associated inner ear abnormalities and will serve as a powerful tool for studying inner ear disorders

Tail pinch induced stress-arousal facilitates brain stimulation reward

Adult male Sprague Dawley rats with chronic access to self stimulation were subjected to handling, tail pinch, or left undisturbed. Tail pinch increased responding for positive reinforcement while the other conditions did not. The stress related properties of tail pinch may therefore facilitate responding in the present and other situations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23691/1/0000661.pd

Stress, behavioral arousal, and open field activity--A reexamination of emotionality in the rat

The effects of stress upon emotionality, and of emotionality upon the open field activity of rats have now been studied for over four decades. Controversy remains however regarding the degree to which stress alters behavior, and the direction of that change. One reason for this is the absence of an adequate behavioral definition of stress. The present series of experiments demonstrates a standard relatively nontraumatic stress induction procedure which may be used in conjunction with open field testing. Pre-exposure to moderately intense light and white noise facilitated open field activity as measured by initial activity, lowered defecation scores, and supplementary measures (rearing, grooming, center field penetration). Further parametric, psychoendocrine, and pharmacological studies characterized the nature of the facilitation, its time course, and its modification by other manipulations. Our results suggest the initial behavioral response to stress in an open field is activation. Previous studies may have differed in their results relating stress and behavior because of subtle procedural distinctions, some of which may be identified using the present technique.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23706/1/0000678.pd

Further studies on a novel animal model of depression: Therapeutic effects of a tricyclic antidepressant

We have previously shown that rats given stress before open field testing have elevated activity in comparison with unstressed rats. This acute behavioral response may be eliminated by chronic stress and restored by pretreatment with the monoamine oxidase inhibitor pargyline. The present study replicated previous findings upon the effects of acute and chronic stress and extended results upon treatment to the class of tricyclic antidepressant drugs, using imipramine as a prototypic tricyclic antidepressant. Imipramine also restored both behavioral and psychoendocrine activity which was otherwise altered by chronic stress.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24331/1/0000598.pd

The effect of survey method on survey participation: Analysis of data from the Health Survey for England 2006 and the Boost Survey for London

BACKGROUND: There is a need for local level health data for local government and health bodies, for health surveillance and planning and monitoring of policies and interventions. The Health Survey for England (HSE) is a nationally-representative survey of the English population living in private households, but sub-national analyses can be performed only at a regional level because of sample size. A boost of the HSE was commissioned to address the need for local level data in London but a different mode of data collection was used to maximise participant numbers for a given cost. This study examines the effects on survey and item response of the different survey modes. METHODS: Household and individual level data are collected in HSE primarily through interviews plus individual measures through a nurse visit. For the London Boost, brief household level data were collected through interviews and individual level data through a longer self-completion questionnaire left by the interviewer and collected later. Sampling and recruitment methods were identical, and both surveys were conducted by the same organisation. There was no nurse visit in the London Boost. Data were analysed to assess the effects of differential response rates, item non-response, and characteristics of respondents. RESULTS: Household response rates were higher in the 'Boost' (61%) than 'Core' (HSE participants in London) sample (58%), but the individual response rate was considerably higher in the Core (85%) than Boost (65%). There were few differences in participant characteristics between the Core and Boost samples, with the exception of ethnicity and educational qualifications. Item non-response was similar for both samples, except for educational level. Differences in ethnicity were corrected with non-response weights, but differences in educational qualifications persisted after non-response weights were applied. When item non-response was added to those reporting no qualification, participants' educational levels were similar in the two samples. CONCLUSION: Although household response rates were similar, individual response rates were lower using the London Boost method. This may be due to features of London that are particularly associated with lower response rates for the self-completion element of the Boost method, such as the multi-lingual population. Nevertheless, statistical adjustments can overcome most of the demographic differences for analysis. Care must be taken when designing self-completion questionnaires to minimise item non-response

Appetitive determinants of self-stimulation

Previous reports have pointed to a biologically meaningful relationship between brain-stimulated reward and appetitive motivation such as feeding. The present experiments further examined this relationship in chronically self-stimulating Sprague-Dawley rats. In Expt 1 restriction of ad libitum food produced a subsequent increase in self-stimulation in the substantia nigra. In Expt 2 restriction of ad libitum self-stimulation, from the same sites, produced a subsequent gain in body weight. In Expt 3 restriction of ad libitum self-stimulation produced subsequent increases in responding for stimulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22562/1/0000107.pd